Technology of absorbable or biodegradable polymers has evolved in many areas over the last years. This is because tissue engineering relies, for the most part, on the use of absorbable scaffold that undergoes mass loss in tandem with tissue formation to replace the absorbing scaffold. While playing a significant role as implants for tissue regeneration especially in bone and cartilage regeneration in extruded and molded solid forms, absorbable polymers are increasingly used in moldable or injectable liquids and gels including suspensions, dispersions and hydrogels.
Many bioabsorbable biomedical polymers rely on the hydrolytic instability of the polymer. Preferably polyester linkage hydrolysis is the responsible mechanism for their in vivo degradation in such polymers (Absorbable and biodegradable polymers, Shalaby and Burg 2004. CRC Press, Advance in polymeric biomaterial series. Chapter 9.5.3).
One major drawback of materials comprising such polymers like poly-L-lactide (PLLA), poly-L-lactic-co-glycolic acid (PLGA), copolymers of PLGA and polyethylene glycol (PEG) polymers is their short shelf-life and storage instability. Already traces of water induce degradation during long term storage and before application of the polymer based material, which might result in undesired features such as segmentation, sedimentation, decomposition, alteration of the viscosity of liquid biomaterials, alteration of the scaffold properties and/or an altered degradation profile in vivo and possible unpredictable results.
WO 2005/105170 discloses a bone substitute material of two components, namely a mineral component and a non-aqueous component, which hardens in an aqueous environment by replacing the non-aqueous component with water. The mineral component e.g. calcium sulfate dihydrate or calcium sulfate hemihydrate disclosed in the bone substitute material functions as a seed which enables to form a cement which strong mechanical properties lacking macroporosity.
In order to overcome this drawback, so far employed conventional methods aim at easy and low cost procedures. One approach employs heating of the used ingredients either alone or in the presence of a catalyst to reduce the water content of the composition. Also treatment with a drying agent and subsequent removal of the drying substance or distillation of solvents such as organic solvents, treating distilled solvents with a drying agent and returning the treated solvent to the system are commonly used as well as distilling out water, binding the distilled water of a solvent with a drying agent and returning the so obtained substance like the solvent to the system.
Alternatively, waterproof packages with or without water drying external agents or dessicants, preferably packages made of plastics and aluminium including blister packages particularly those with a reduced water vapor permeability are a preferred packaging form for solid or semi-solid and liquid pharmaceutical preparations which are moisture sensitive as is e.g. described in EP 0 779 872 and references therein incorporated by reference herewith.
However, in order to prepare and to maintain water free polymer based materials such as liquid polymer solutions, polymer dispersions, polymer melts and liquid polymer based materials, known methods including thermal pretreatment of ingredients, vacuum drying, lyophillisation, molecular sieve as well as using a packaging system with desiccants for packaging moisture sensitive pharmaceutical preparations have been unsuccessful. Further improvements have been required for the step of avoiding polymer degradation upon storage of the material by removing water from the composition.
Accordingly, it is one object underlying the present invention to provide alternative means to prepare and to maintain water free polymer based materials (i.e. materials comprising polymers such as liquid polymer solutions, polymer dispersions, polymer melts and liquid polymer based materials).
Moreover, it is another object underlying the present invention to provide alternative means for inhibiting water induced polymer degradation in a polymer based material, which means preferably increase storage stability in a polymer comprising material such as liquid polymer solutions, polymer dispersions, polymer melts and liquid polymer based materials.
Furthermore, it is another object underlying the present invention to provide means for inhibiting of water induced polymer degradation in a polymer based material, which can be applied in cases, wherein conventionally used methods as listed above are not suitable, cumbersome, expensive or laborious.
Alternatively, the object underlying the present invention was to provide a polymer comprising material exhibiting improved shelf-life time, in which the degradation of the polymer is prevented or inhibited during storage, i.e. before use.
Another object underlying the present invention was to provide a polymer comprising material exhibiting improved shelf-life time for tissue regeneration, which forms a sponge-like matrix.
Another object underlying the present invention was to provide a polymer comprising material with increased shelf-life time for tissue regeneration including periodontal attachment or tissue regeneration.
Another object underlying the present invention was to provide a material for inducing blood clot formation or blood clot stabilization.
Another object underlying the present invention was to provide a polymer comprising material for periodontal tissue regeneration and a method for using it.